OPRR Public Health Service Policy on Humane Care and Use of Laboratory Animals U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health Revised as of September 1986 HEALTH RESEARCH EXTENSION ACT OF 1985 PUBLIC LAW 99-158, November 20, 1985 "ANIMALS IN RESEARCH" "Sec. 495. (a) The Secretary, acting through the Director of NIH, shall establish guidelines for the following: "(1) The proper care of animals to be used in biomedical and behavioral research. "(2) The proper treatment of animals while being used in such research. Guidelines under this paragraph shall require- "(A) the appropriate use of tranquilizers, analgesics, anesthetics, paralytics, and euthanasia for animals in such research; and "(B) appropriate presurgical and post-surgical veterinary medical and nursing care for animals in such research. Such guidelines shall not be construed to prescribe methods of research. "(3) The organization and operation of animal care committees in accordance with subsection (b). "(b)(1) Guidelines of the Secretary under subsection (a)(3) shall require animal care committees at each entity which conducts biomedical and behavioral research with funds provided under this Act (including the National Institutes of Health and the national research institutes) to assure compliance with the guidelines established under subsection (a). "(2) Each animal care conunittee shall be appointed by the chief executive officer of the entity for which the committee is established, shall be composed of not fewer than three members, and shall include at least one individual who has no association with such entity and at least one doctor of veterinary medicine. "(3) Each animal care committee of a research entity shall- "(A) review the care and treatment of animals in all animal study areas and facilities of the research entity at least semiannually to evaluate compliance with applicable guidelines established under subsection (a) for appropriate animal care and treatment; "(B) keep appropriate records of reviews conducted under sub-paragraph (A); and "(C) for each review conducted under subparagraph (A), file with the Director of NIH at least annually (i) a certification that the review has been conducted, and (ii) reports of any violations of guidelines established under subsection (a) or assurances required under paragraph (1) which were observed in such review and which have continued after notice by the committee to the research entity involved of the violations. Reports filed under subparagraph (C) shall include any minority views filed by members of the committee. "(c) The Director of NIH shall require each applicant for a grant, contract, or cooperative agreement involving research on animals which is administered by the National Institutes of Health or any national research institute to include in its application or contract proposal, submitted after the expiration of the twelve-month period beginning on the date of enactment this section- "(1) assurances satisfactory to the Director of NIH that- "(A) the applicant meets the requirements of the guidelines established under paragraphs (1) and (2) of subsection (a) and has an animal care committee which meets the requirements of subsection (b); and "(B) scientists, animal technicians, and other personnel involved with animal care, treatment, and use by the appheant have available to them instruction or training in the humane practice of animal maintenance and experimentation, and the concept, availability, and use of research or testing methods that li@t the use of animals or limit animal distress; and "(2) a statement of the reasons for the use of animals in the research to be conducted with funds provided under such grant or contract. Notwithstanding subsection (a)(2) of section 553 of title 5, United States Code, regulations under this subsection shall be promulgated in accordance with the notice and comment requirements of such section. "(d) If the Director of NIH determines that- "(1) the conditions of animal care, treatment, or use in an entity which is receiving a grant, contract, or cooperative agreement involving research on animals under this title do not meet applicable guidelines established under subsection (a); "(2) the entity has been notified by the Director of NIH of such determination and has been given a reasonable opportunity to take corrective action; and "(3) no action has been taken by the entity to correct such conditions; the Director of NIH shall suspend or revoke such grant or contract under such conditions as the Director determines appropriate. "(e) No guideline or regulation promulgated under subsection (a) or (c) may require a research entity to disclose publicly trade secrets or commercial or financial information which is privileged or confidential." LOCATION OF DOCUMENTS DOCUMENT PAGE Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . .i Table of Contents for the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals . . . . . . . .iii Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals. . . . . . . . . . . . . . . . .1 Instructions for Implementation of the Amended Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals. . . . . . . . . . . . . . . . . . . . 18 Sample Animal Welfare Assurance. . . . . . . . . . . . . . . . 22 U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. . . . . . . . . . . . . . . . . . . 33 SUMMARY This amended version of the Public Health Service Policy on Humane Care and Use of Laboratory Animals by Awardee Institutions, now entitled Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, incorporates the changes in the Public Health Service Act (PHS Act) mandated by the Health Research Extension Act of l985, Public Law 99-l58. The amended Policy also contains various minor editorial changes, including both technical and clarifying amendments to the original Policy. All applications and proposals for award, which are either submitted to the PHS on or after November 1, 1986, or being conducted on or after July 1, 1987, must meet the requirements of the PHS Policy as amended. Institutions which currently have an approved or provisionally-acceptable Animal Welfare Assurance on file with the Office for Protection from Research Risks (OPRR) must submit to OPRR by July 1, 1987, a document in the form of an appendix or amendment which states the changes that the institution has made to conform to the amended Public Health Service Policy. The most significant changes required by the Health Research Extension Act are: ø The Policy will now apply to research that the Public Health Service (PHS) conducts intramurally. ø The Institutional Animal Care and Use Committee (IACUC) will be appointed by the Chief Executive Officer of the Institution. This change is required by Section 495(b)(2) of the PHS Act. ø The Policy now requires that the program description of the Assurance include an explanation of the training or instruction available to scientists, animal technicians, and other personnel involved in animal care, treatment, or use. The training or instruction must include information on the humane practice of animal care and use and the concept, availability, and use of research or testing methods that minimize the number of animals required to obtain valid results and minimize animal distress. This change is mandated by Section 495(c)(1)(B) of the PHS Act. ø The IACUC now must reevaluate and prepare reports on all of the institution's programs and facilities (including satellite facilities) for activities involving animals at least twice, instead of once, each year. This change is in accordance with Section 495(b)(3)(A) of the PHS Act. ø The IACUC, through the Institutional Official, shall be responsible for reporting requirements. This language change reflects the language used in Section 495(b)(3) of the PHS Act. ø Minority views filed by members of the IACUC must be included in reports filed under IV.F. of this Policy. The last sentence of Section 495(b)(3) of the PHS Act requires this change. PUBLIC HEALTH SERVICE (PHS) POLICY ON HUMANE CARE AND USE OF LABORATORY ANIMALS Table of Contents I. Introduction. . . . . . . . . . . . . . . . . . . . . . . 1 II. Applicability and Effective Dates . . . . . . . . . . . . 1 III. Definitions . . . . . . . . . . . . . . . . . . . . . . . 2 IV. Implementation by Institutions. . . . . . . . . . . . . . 3 A. Animal Welfare Assurance. . . . . . . . . . . . . . . 3 1. Institutional Program for Animal Care and Use . . . 4 2. Institutional Status. . . . . . . . . . . . . . . . 5 3. Institutional Animal Care and Use Committee (IACUC) 6 B. Functions of the Institutional Animal Care and Use Committee (IACUC). . . . . . . . . . . . . . . . 7 C. Review of PHS-Conducted or Supported Research Projects . . . . . . . . . . . . . . . . . . . . . . 9 D. Information Required in Applications and Proposals for Awards Submitted to PHS. . . . . . . . . . . . .12 1. All Institutions. . . . . . . . . . . . . . . . . .12 2. Institutions That Have an Approved or Provisionally-Acceptable Assurance. . . . . . . . .13 3. Institutions That Do Not Have an Approved or Provisionally-Acceptable Assurance. . . . . . . . .13 E. Recordkeeping Requirements. . . . . . . . . . . . . .14 F. Reporting Requirements. . . . . . . . . . . . . . . .15 V. Implementation by PHS . . . . . . . . . . . . . . . . . .16 A. Responsibilities of the Office for Protection from Research Risks (OPRR). . . . . . . . . . . . . .16 B. Responsibilities of PHS Awarding Units. . . . . . . .16 C. Conduct of Special Reviews/Site Visits. . . . . . . .17 D. Waiver. . . . . . . . . . . . . . . . . . . . . . . .17 PUBLIC HEALTH SERVICE (PHS) POLICY ON HUMANE CARE AND USE OF LABORATORY ANIMALS I. Introduction It is the Policy of the Public Health Service (PHS) to require institutions to establish and maintain proper measures to ensure the appropriate care and use of all animals involved in research, research training, and biological testing activities (hereinafter referred to as activities) conducted or supported by the PHS. The PHS endorses the "U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training" developed by the Interagency Research Animal Committee (IRAC). This Policy is intended to implement and supplement those Principles. II. Applicability and Effective Dates This Policy is applicable to all PHS-conducted or supported activities involving animals, whether the activities are performed at a PHS agency, an awardee institution, or any other institution and conducted in the United States, the Commonwealth of Puerto Rico, or any territory or possession of the United States. The requirements of this Policy are effective for applications and proposals for PHS research and research training awards involving animals that are submitted for PHS consideration on or after November 1, 1986, and for all PHS-conducted or supported research and research training activities involving animals that are being conducted on or after July 1, 1987. Institutions in foreign countries receiving PHS support for activities involving animals shall comply with this Policy, or provide evidence to the PHS that acceptable standards for the humane care and use of the animals in PHS-conducted or supported activities will be met. No PHS support for an activity involving animals will be provided to an individual unless that individual is affiliated with or sponsored by an institution which can and does assume responsibility for compliance with this Policy, unless the individual makes other arrangements with the PHS. This Policy does not affect applicable state or local laws or regulations which impose more stringent standards for the care and use of laboratory animals. All institutions are required to comply, as applicable, with the Animal Welfare Act, and other Federal statutes and regulations relating to animals. III. Definitions A. Animal Any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes. B. Animal Facility Any and all buildings, rooms, areas, enclosures, or vehicles, including satellite facilities, used for animal confinement, transport, maintenance, breeding, or experiments inclusive of surgical manipulation. A satellite facility is any containment outside of a core facility or centrally designated or managed area in which animals are housed for more than 24 hours. C. Animal Welfare Act Public Law 89-544, l966, as amended, (P.L. 9l-579, P.L. 94-279 and P.L. 99-l98) 7 U.S.C. 2l3l et. seq. Implementing regulations are published in the Code of Federal Regulations (CFR), Title 9, Subchapter A, Parts l, 2, 3, and 4, and are administered by the U.S. Department of Agriculture. D. Animal Welfare Assurance or Assurance The documentation from an institution assuring institutional compliance with this Policy. E. Guide Guide for the Care and Use of Laboratory Animals (Guide), HHS, NIH Pub. No. 85-23, l985 edition or succeeding revised editions. F. Institution Any public or private organization, business, or agency (including components of Federal, state, and local governments). G. Institutional Official An individual who signs, and has the authority to sign the institution's Assurance, making a commitment on behalf of the institution that the requirements of this Policy will be met. H. Public Health Service The Public Health Service or PHS includes the Alcohol, Drug Abuse, and Mental Health Administration; the Centers for Disease Control; the Food and Drug Administration; the Health Resources and Services Administration; the National Institutes of Health; and the Office of the Assistant Secretary for Health, Department of Health and Human Services. I. Quorum A majority of the members of the Institutional Animal Care and Use Committee (IACUC). IV. Implementation by Institutions A. Animal Welfare Assurance No activity involving animals may be conducted or supported by the PHS until the institution conducting the activity has provided a written Assurance acceptable to the PHS, setting forth compliance with this Policy. Assurances shall be submitted to the Office for Protection from Research Risks (OPRR), Office of the Director, National Institutes of Health, 9000 Rockville Pike, Building 3l, Room 4B09, Bethesda, Maryland 20892. The Assurance shall be typed on the institution's letterhead and signed by the Institutional Official. OPRR will provide the institution with necessary instructions and an example of an acceptable Assurance. All Assurances submitted to the PHS in accordance with this Policy will be evaluated by OPRR to determine the adequacy of the institution's proposed program for the care and use of animals in PHS-conducted or supported activities. On the basis of this evaluation OPRR may approve or disapprove the Assurance, or negotiate an approvable Assurance with the institution. Approval of an Assurance will be for a specified period of time (no longer than five years) after which time the institution must submit a new Assurance to OPRR. OPRR may limit the period during which any particular approved Assurance shall remain effective or otherwise condition, restrict, or withdraw approval. Without an applicable PHS-approved or provisionally-acceptable Assurance no PHS-conducted or supported activity involving animals at the institution will be permitted to continue. 1. Institutional Program for Animal Care and Use The Assurance shall fully describe the institution's program for the care and use of animals in PHS-conducted or supported activities. The PHS requires institutions to use the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for developing and implementing an institutional program for activities involving animals. The program description must include the following: a. a list of every branch and major component of the institution, as well as a list of every branch and major component of any other institution, which is to be included under the Assurance; b. the lines of authority and responsibility for administering the program and ensuring compliance with this Policy; c. the qualifications, authority, and responsibility of the veterinarian(s) who will participate in the program and the percent of time each will contribute to the program; d. the membership list of the Institutional Animal Care and Use Committee(s)(1) (IACUC) established in accordance with the requirements set forth in IV.A.3. of this Policy; e. the procedures which the IACUC will follow to fulfill the requirements set forth in this Policy; f. the health program for personnel who work in laboratory animal facilities or have frequent contact with animals; g. a synopsis of training or instruction in the humane prac tice of animal care and use, as well as training or instruction in research or testing methods that minimize the number of animals required to obtain valid results and minimize animal distress, offered to scientists, animal technicians, and other personnel involved in animal care, treatment, or use; h. the gross square footage of each animal facility (including satellite facilities), the species housed therein and the average daily inventory, by species, of animals in each facility; and i. any other pertinent information requested by OPRR. 2. Institutional Status Each institution must assure that its program and facilities are in one of the following categories: Category 1 - Accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC). All of the institution's programs and facilities (including satellite facilities) for activities involving animals have been evaluated and accredited by AAALAC, or another accrediting body recognized by PHS(2). All of the institution's programs and facilities (including satellite facilities) for activities involving animals have also been evaluated by the IACUC and will be reevaluated by the IACUC at least once every six months, in accordance with IV.B.1. and 2. of this Policy, and reports prepared in accordance with IV.B.3. of this Policy. (Footnote 1: The name Institutional Animal Care and Use Committee (IACUC) as used in this Policy is intended as a generic term for a committee whose function is to ensure that the care and use of animals in PHS-conducted or supported activities is appropriate and humane in accordance with this Policy. However, each institution may identify the committee by whatever name it chooses). (Footnote 2: As of the issuance date of this Policy, the only accrediting body recognized by PHS is the American Association for Accreditation of Laboratory Animal Care (AAALAC)). Category 2 - Evaluated by the Institution. All of the institution's programs and facilities (including satellite facilities) for activities involving animals have been evaluated by the IACUC and will be reevaluated by the IACUC at least once every six months, in accordance with IV.B.1. and 2. of this Policy, and reports prepared in accordance with IV.B.3. of this Policy. The initial report of the IACUC evaluation shall be submitted to OPRR with the Assurance. 3. Institutional Animal Care and Use Committee (IACUC) a. The Chief Executive Officer shall appoint an Institutional Animal Care and Use Committee (IACUC), qualified through the experience and expertise of its members to oversee the institution's animal program, facilities, and procedures. b. The Assurance must include the names, position titles, and credentials of the IACUC chairperson and the members. The committee shall consist of not less than five members, and shall include at least: (l) one Doctor of Veterinary Medicine, with training or experience in laboratory animal science and medicine, who has direct or delegated program responsibility for activities involving animals at the institution; (2) one practicing scientist experienced in research involving animals; (3) one member whose primary concerns are in a nonscientific area (for example, ethicist, lawyer, member of the clergy); and (4) one individual who is not affiliated with the institution in any way other than as a member of the IACUC, and is not a member of the immediate family of a person who is affiliated with the institution. c. An individual who meets the requirements of more than one of the categories detailed in IV.A.3.b.(l)-(4) of this Policy may fulfill more than one requirement. However, no committee may consist of less than five members. B. Functions of the Institutional Animal Care and Use Committee (IACUC) As an agent of the institution, the IACUC shall with respect to PHS-conducted or supported activities: l. review at least once every six months the institution's program for humane care and use of animals, using the Guide as a basis for evaluation; 2. inspect at least once every six months all of the institution's animal facilities (including satellite facilities) using the Guide as a basis for evaluation; 3. prepare reports of the IACUC evaluations conducted as required by IV.B.1. and 2. of this Policy, and submit the reports to the Institutional Official(3). (NOTE: the reports shall be updated at least once every six months upon completion of the required semiannual evaluations and shall be maintained by the institution and made available to OPRR upon request. The reports must contain a description of the nature and extent of the institution's adherence to the Guide and this Policy and must identify specifically any departures from the provisions of the Guide and this Policy, and must state the reasons for each departure. The reports must distinguish significant deficiencies from minor deficiencies. A significant deficiency is one which, consistent with this Policy, and, in the judgment of the IACUC and the Institutional Official, is or may be a threat to the health or safety of the animals. If program or facility deficiencies are noted, the reports must contain a reasonable and specific plan and schedule for correcting each deficiency. If some or all of the institution's facilities are accredited by AAALAC or another accrediting body recognized by PHS, the report should identify those facilities as such.); 4. review concerns involving the care and use of animals at the institution; 5. make recommendations to the Institutional Official regarding any aspect of the institution's animal program, facilities, or personnel training; 6. review and approve, require modifications in (to secure approval) or withhold approval of those components of PHS-conducted or supported activities related to the care and use of animals as specified in IV.C. of this Policy; 7. review and approve, require modifications in (to secure approval), or withhold approval of proposed significant changes regarding the use of animals in ongoing activities; and 8. be authorized to suspend an activity involving animals in accordance with the specifications set forth in IV.C.6 of this Policy. (Footnote 3: The Institutional Animal Care and Use Committee (IACUC) may, at its discretion, determine the best means of conducting an evaluation of the institution's programs and facilities. the IACUC may invite ad hoc consultants to assist in conducting the evaluation. However, the IACUC remains responsible for the evaluation and report). C. Review of PHS-Conducted or Supported Research Projects 1. In order to approve proposed research projects or proposed significant changes in ongoing research projects, the IACUC shall conduct a review of those components related to the care and use of animals and determine that the proposed research projects are in accordance with this Policy. In making this determination, the IACUC shall confirm that the research project will be conducted in accordance with the Animal Welfare Act insofar as it applies to the research project, and that the research project is consistent with the Guide unless acceptable justification for a departure is presented. Further, the IACUC shall determine that the research project conforms with the institution's Assurance and meets the following requirements: a. Procedures with animals will avoid or minimize discomfort, distress, and pain to the animals, consistent with sound research design. b. Procedures that may cause more than momentary or slight pain or distress to the animals will be performed with appropriate sedation, analgesia, or anesthesia, unless the procedure is justified for scientific reasons in writing by the investigator. c. Animals that would otherwise experience severe or chronic pain or distress that cannot be relieved will be painlessly sacrificed at the end of the procedure or, if appropriate, during the procedure. d. The living conditions of animals will be appropriate for their species and contribute to their health and comfort. The housing, feeding, and nonmedical care of the animals will be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. e. Medical care for animals will be available and provided as necessary by a qualified veterinarian. f. Personnel conducting procedures on the species being maintained or studied will be appropriately qualified and trained in those procedures. g. Methods of euthanasia used will be consistent with the recommendations of the American Veterinary Medical Association (AVMA) Panel on Euthanasia(4), unless a deviation is justified for scientific reasons in writing by the investigator. (Footnote 4: Journal of the American Veterinary Medical Association (JAVMA), 1986, Vol. 188, No. 3, pp. 252-268, or succeeding revised editions). 2. Prior to the review, each IACUC member shall be provided with a list of proposed research projects to be reviewed. Written descriptions of research projects that involve the care and use of animals shall be available to all IACUC members, and any member of the IACUC may obtain, upon request, full committee review of those research projects. If full committee review is not requested, at least one member of the IACUC, designated by the chairperson and qualified to conduct the review, shall review those research projects and have the authority to approve, require modifications in (to secure approval) or request full committee review of those research projects. If full committee review is requested, approval of those research projects may be granted only after review at a convened meeting of a quorum of the IACUC and with the approval vote of a majority of the quorum present. No member may participate in the IACUC review or approval of a research project in which the member has a conflicting interest (e.g., is personally involved in the project) except to provide information requested by the IACUC; nor may a member who has a conflicting interest contribute to the constitution of a quorum. 3. The IACUC may invite consultants to assist in the review of complex issues. Consultants may not approve or withhold approval of an activity or vote with the IACUC unless they are also members of the IACUC. 4. The IACUC shall notify investigators and the institution in writing of its decision to approve or withhold approval of those activities related to the care and use of animals, or of modifications required to secure IACUC approval. If the IACUC decides to withhold approval of an activity, it shall include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing. 5. The IACUC shall conduct continuing review of activities covered by this Policy at appropriate intervals as determined by the IACUC, but not less than once every three years. 6. The IACUC may suspend an activity that it previously approved if it determines that the activity is not being conducted in accordance with applicable provisions of the Animal Welfare Act, the Guide, the institution's Assurance, or IV.C.l.a.-g. of this Policy. The IACUC may suspend an activity only after review of the matter at a convened meeting of a quorum of the IACUC and with the suspension vote of a majority of the quorum present. 7. If the IACUC suspends an activity involving animals, the Institutional Official in consultation with the IACUC shall review the reasons for suspension, take appropriate corrective action, and report that action with a full explanation to OPRR. 8. Applications and proposals that have been approved by the IACUC may be subject to further appropriate review and approval by officials of the institution. However, those officials may not approve an activity involving the care and use of animals if it has not been approved by the IACUC. D. Information Required in Applications and Proposals for Awards Submitted to PHS 1. All Institutions Applications and proposals (competing and non-competing) for awards submitted to PHS that involve the care and use of animals shall contain the following information: a. identification of the species and approximate number of animals to be used; b. rationale for involving animals, and for the appropriateness of the species and numbers to be used; c. a complete description of the proposed use of the animals; d. a description of procedures designed to assure that discomfort and injury to animals will be limited to that which is unavoidable in the conduct of scientifically valuable research, and that analgesic, anesthetic, and tranquilizing drugs will be used where indicated and appropriate to minimize discomfort and pain to animals; and e. a description of any euthanasia method to be used. Non-competing applications and contract proposals for other than full and open competitions need not repeat the information required by IV.D.1.a.-e. if the information was complete in the last competing application or proposal and there are no significant changes to that information. However, the application or proposal must contain a statement to that effect. If there are significant changes in the information, then the application or proposal must specifically identify them and state the reasons for the changes. 2. Institutions That Have an Approved or Provisionally Acceptable Assurance Applications or proposals (competing and non-competing) covered by this Policy from institutions which have an approved or provisionally acceptable Assurance on file with OPRR shall include verification of approval (including the date of the most recent approval) by the IACUC of those components related to the care and use of animals. With the authorization of PHS, such verification may be filed at a time not to exceed 60 days after submission of applications or proposals(5). If verification of IACUC approval is submitted subsequent to the submission of the application or proposal, the verification shall state the modifications, if any, required by the IACUC. The verification shall be signed by an individual authorized by the institution, but need not be signed by the Institutional Official. 3. Institutions That Do Not Have an Approved or Provisionally Acceptable Assurance Applications and proposals covered by this Policy from institutions that do not have an approved or provisionally acceptable Assurance on file with OPRR shall contain a declaration that the institution will establish an IACUC and submit an Assurance upon request by OPRR. After OPRR has requested the Assurance, the institution shall prepare an Assurance in accordance with IV.A. of this Policy and the established IACUC shall review those components of the application or proposal as required by IV.C. of this Policy. The institution shall then submit to OPRR the Assurance and verification of IACUC approval. The verification shall state the modifications, if any, required by the IACUC. The verification shall be signed by an individual authorized by the institution, but need not be signed by the Institutional Official who signed the Assurance. E. Recordkeeping Requirements 1. The awardee institution shall maintain: a. an Assurance which has been either approved or deemed provisionally acceptable by the PHS; b. minutes of IACUC meetings, including records of attendance, activities of the committee, and committee deliberations; c. records of applications, proposals, and proposed significant changes in the care and use of animals and whether IACUC approval was given or withheld; (Footnote 5: Until further notice, PHS hereby authorizes all institutions with approved or provisionally-acceptable Assurances to file verification of IACUC approval either along with the competing appliication or proposal or within 60 days of submission of the application or proposal. From time to time PHS will reevaluate this blanket authorization. Any decision to withdraw this authorization will take place only after ample opportunity is provided for comment by the public). d. records of semiannual IACUC reports and recommendations (including minority views) as forwarded to the Institutional Official; and e. records of accrediting body determinations. 2. All records shall be maintained for at least three years; records that relate directly to applications, proposals, and proposed significant changes in ongoing activities reviewed and approved by the IACUC shall be maintained for the duration of the activity and for an additional three years after completion of the activity. All records shall be accessible for inspection and copying by authorized OPRR or other PHS representatives at reasonable times and in a reasonable manner. F. Reporting Requirements 1. At least once every 12 months, the IACUC, through the Institutional Official, shall report in writing to OPRR: a. any change in the institution's program or facilities which would place the institution in a different category than specified in its Assurance (see IV.A.2. of this Policy); b. any change in the description of the institution's program for animal care and use as required by IV.A.1.a.-i. of this Policy; c. any changes in the IACUC membership; and d. notice of the dates that the IACUC conducted its semiannual evaluations of the institution's program and facilities and submitted the evaluations to the Institutional Official. 2. At least once every 12 months, the IACUC, at an institution which has no changes to report as specified in IV.F.l. a.-c. of this Policy, shall submit a letter, through the Institutional Official, to OPRR stating that there are no changes and informing OPRR of the dates of the required IACUC evaluations and submissions to the Institutional Official. 3. The IACUC, through the Institutional Official, shall promptly provide OPRR with a full explanation of the circumstances and actions taken with respect to: a. any serious or continuing noncompliance with this Policy; b. any serious deviation from the provisions of the Guide; or c. any suspension of an activity by the IACUC. 4. Reports filed under IV.F. of this Policy shall include any minority views filed by members of the IACUC. V. Implementation by PHS A. Responsibilities of the Office for Protection from Research Risks (OPRR) OPRR is responsible for the general administration and coordination of this Policy and will: 1. request and negotiate, approve or disapprove, and, as necessary, restrict or withdraw approval of Assurances; 2. distribute to executive secretaries of initial review and technical evaluation groups, and to PHS awarding units, lists of institutions that have an approved Assurance; 3. advise awarding units and awardee institutions concerning the implementation of this Policy; 4. evaluate allegations of noncompliance with this Policy; 5. have the authority to review and approve or disapprove waivers to this Policy (see V.D. of this Policy); and 6. conduct site visits to selected institutions. B. Responsibilities of PHS Awarding Units PHS awarding units may not make an award for an activity involving animals unless the prospective awardee institution and all other participating institutions have approved or provisionally acceptable Assurances on file with OPRR, and the awardee institution has provided verification of approval by the IACUC of those components of the application or proposal related to the care and use of animals. If any one of these institutions does not have an approved or provisionally-acceptable Assurance on file with OPRR, the awarding unit will ask OPRR to negotiate an Assurance with the institution(s) before an award is made. No award shall be made until all required Assurances have been submitted by the institution(s), been approved or designated provisionally acceptable by OPRR, and the institution(s) have provided verification of approval by the IACUC of those components of the application or proposal related to the care and use of animals. C. Conduct of Special Reviews/Site Visits Each awardee institution is subject to review at any time by PHS staff and advisors, which may include a site visit, in order to assess the adequacy or accuracy of the institution's compliance or expressed compliance with this Policy. D. Waiver Institutions may request a waiver of a provision or provisions of this Policy by submitting a request to OPRR. No waiver will be granted unless sufficient justification is provided and the waiver is approved in writing by OPRR. INSTRUCTIONS FOR IMPLEMENTATION OF THE AMENDED PUBLIC HEALTH SERVICE (PHS) POLICY ON HUMANE CARE AND USE OF LABORATORY ANIMALS The Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, incorporating the changes mandated by the Health Research Extension Act of 1985, will become effective November 1, 1986. Institutions which currently have an approved or provisionally-acceptable Animal Welfare Assurance on file with the Office for Protection from Research Risks (OPRR) must submit to OPRR by July 1, 1987, a document in the form of an appendix or amendment which states the changes that the institution has made in order to conform to the amended PHS Policy. These institutions are to begin implementing this Policy as soon as possible and are expected to begin operating under the amended Policy no later than November 1, 1986. All applications and proposals for award which are either submitted to the PHS on or after November 1, 1986, or being conducted on or after July 1, 1987, must meet the requirements of the PHS Policy as amended. Section IV.D. of the Policy requires all applications and proposals to contain specific information regarding the proposed use of laboratory animals. Applications and proposals submitted to PHS that do not contain the information required in Section IV.D. of this Policy will be considered considered incomplete and may be deferred for a later review. (The information required by Section IV.D.1. of this Policy should appear in the appropriate component of each application or proposal, for example, Section 2.F. of the PHS Grant Application Form 398.) Institutions That Have an Approved or Provisionally Acceptable Assurance Applications and proposals for award (competing and non-competing) submitted to the PHS must contain verification that the Institutional Animal Care and Use Committee (IACUC) has approved those components of the application or proposal related to the care and use of laboratory animals. PHS prefers that verification of IACUC approval be submitted along with the application or proposal, however, it may be submitted within 60 days of submission of the application or proposal. If verification of IACUC approval is submitted subsequent to the submission of the application or proposal, the verification must state any modifications required by the IACUC. In the near future, PHS will institute a standardized method for institutional submission of IACUC approval. In the interim, verification of IACUC approval must be submitted via a letter from the institution to the PHS. The letter must be signed by either the Institutional Official who signed the institution's Animal Welfare Assurance or by another individual authorized by the institution to provide verification of IACUC approval. The following example may be used in preparing such letters of verification: EXAMPLE OF ACCEPTABLE VERIFICATION LETTER Date Division of Research Grants* National Institutes of Health 5333 Westbard Avenue Westwood Building, Room 240 Bethesda, MD 20205 Dear Sir: The following application submitted to the Public Health Service was reviewed and approved by this Institution's Animal Care and Use Committee on (insert date of approval). Title of Application: Name of Principal Investigator: Name of Institution: This institution has an Animal Welfare Assurance on file with the Office for Protection from Research Risks. The Assurance number is . (Insert old Assurance number until a new Assurance number is assigned.) As a condition of approval, this Institution's Animal Care and Use Committee (IACUC) required the following modifications to the above-referenced referenced application:** (Signature) (Title) * This address should be used for submission with grant applications. If verification is submitted subsequent to the submission of the application, it should be addressed to the Executive Secretary of the initial review group designated on the card returned to the institution acknowledging receipt of the application. For noncompeting grant applications, verification should be addressed to the appropriate Program Administrator Grants Management Officer. For contract proposals, verification should be addressed to the Contract Officer. ** This information is required when the modifications are not reflected in the grant application or contract proposal. Institutions That Do Not Have an Approved or Provisionally Acceptable Assurance Institutions that do not have an approved or provisionally acceptable Animal Welfare Assurance on file with OPRR must submit, with the application or proposal, a declaration that the institution will establish an Institutional Animal Care and Use Committee and submit an Assurance upon request by OPRR. The following letter is an example of an Acceptable Declaration Letter: EXAMPLE OF AN ACCEPTABLE DECLARATION LETTER Date Division of Research Grants* National Institutes of Health 3333 Westbard Avenue Westwood Building, Room 240 Bethesda, MD 20205 Dear Sir: This institution does not have an Animal Welfare Assurance on file with the Office for Protection from Research Risks (OPRR) to cover the following application: Title of Application: Name of Principal Investigator: Name of Institution: This institution will establish an Institutional Animal Care and Use Committee (IACUC), have the application reviewed by the IACUC and submit an Animal Welfare Assurance, upon request, to OPRR. (Signed by Institutional Official) (Title) * For contract proposals, this letter should be addressed to the Contract Officer. When appropriate, OPRR will request that the institution submit an Assurance. The Institutional Animal Care and Use Committee (IACUC) must review those sections of the application or proposal related to the care and use of animals and submit the Assurance and verification of IACUC approval to OPRR. The Example of an Acceptable Verification Letter (see preceding page of this document) may be followed in submitting verification of IACUC approval. NOTE: After January 1, 1986, all sections of applications and proposals related to the care and use of live vertebrate animals must be reviewed and approved by an IACUC before PHS will award funds for an activity involving animals. SAMPLE ANIMAL WELFARE ASSURANCE Background Information A sample Animal Welfare Assurance has been prepared by the Office for Protection from Research Risks to assist institutions in developing an Assurance in accordance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (see pps. 19-26 of this document). This sample Assurance includes all of the necessary elements for compliance with the PHS Policy. There are several areas in an Assurance which require that the institution provide specific information regarding procedures, policies, and the responsibilities and qualifications of the personnel of the institution. The Animal Welfare Assurance will need to be tailored to meet the administrative and research requirements for each institution. This sample Assurance document provides suggestions and examples of the kind of information that is to be provided by the institution in accordance with this PHS Policy. The sample refers to an Institutional Animal Care and Use Committee (IACUC), a generic name for the institutional committee established in accordance with the PHS Policy to fulfill the functions outlined in the Policy. In preparing its Assurance document each institution should consistently use whatever name it has assigned to that committee. More than one IACUC may be established to meet the needs of an institution. The Assurance must identify each IACUC established by the institution. This sample is intended to aid your institution in developing an Animal Welfare Assurance. Please note that the text of the sample Assurance contains regular type as well as italics. The italic print indicates where you should provide information specific to your institution. Close adherence to the format will facilitate the review process. Questions should be directed to the Office for Protection from Research Risks, Policy and Assurance Staff, National Institutes of Health, Building 3l, Room 4B09, Bethesda, Maryland, 20892, (30l) 496-7041. INSTITUTIONAL LETTERHEAD (Name of Institution) Assurance of Compliance with Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (Name of Institution), hereinafter referred to as institution, hereby gives assurance that it will comply with the Public Health Service Policy on Humane Care and Use of Laboratory Animals, hereinafter referred to as PHS Policy. I. Applicability This Assurance is applicable to all research, research training, experimentation, and biological testing and related activities, herein-after referred to as activities, involving live, vertebrate animals supported by the Public Health Service (PHS) and conducted at this institution, or at another institution as a consequence of the sub-granting or subcontracting of a PHS-conducted or supported activity by this institution. "Institution" includes the following branches and major components of (name of institution) (list every branch and major component covered by this Assurance). (If applicable), "Institution" also includes the following branches and major components of (name(s) of any other institution(s) to be included under this Assurance) (list every branch and major component of other institution(s) to be covered by this Assurance). II. Institutional Policy A. This institution will comply with all applicable provisions of the Animal Welfare Act and other Federal statutes and regulations relating to animals. B. This institution is guided by the "U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training." C. This institution acknowledges and accepts responsibility for the care and use of animals involved in activities covered by this Assurance. As partial fulfillment of this responsibility this institution will make a reasonable effort to ensure that all individuals involved in the care and use of laboratory animals understand their individual and collective responsibilities for compliance with this Assurance as well as all otherapplicable laws and regulations pertaining to animal care and use. D. This institution has established and will maintain a program for activities involving animals in accordance with the Guide for the Care and Use of Laboratory Animals (Guide). III. Institutional Program for Animal Care and Use A. The lines of authority and responsibility for administering the program and ensuring compliance with this Policy are: (Describe or diagram the organization of the administration and staff, including the Institutional Animal Care and Use Committee, the Institutional Official, and the veterinarian.) B. The qualifications, authority, and percent of time contributed by veterinarian(s) who will participate in the program are: (Indicate professional or academic degrees and the number of years of pertinent training or experience in laboratory animal medicine. Describe the veterinarians' functions, percentage of time contribution and responsibilities insofar as they relate to implementation of this Policy and the recommendations in the Guide for the Care and Use of Laboratory Animals.) C. This institution has established an Institutional Animal Care and Use Committee (IACUC), which is qualified through the experience and expertise of its members to oversee the institution's animal program, facilities, and procedures. The IACUC consists of at least five members, and its membership meets the compositional requirements set forth in the PHS Policy at IV.A.3.b. Attached is a list of the names, position titles, earned degrees and other credentials of the IACUC chairperson and members. D. The IACUC will: 1. Review at least once every six months the institution's program for humane care and use of animals, using the Guide as a basis for evaluation. 2. Inspect at least once every six months all of the institution's animal facilities (including satellite facilities) using the Guide as a basis for evaluation. 3. Prepare reports of the IACUC evaluations as set forth in the PHS Policy at IV.B.3. and submit the reports to (insert name or title of the Institutional Official signing the Assurance). 4. Review concerns involving the care and use of animals at the institution. 5. Make written recommendations to (insert name or title of the Institutional Official signing the Assurance) regarding any aspect of the institution's animal program, facilities, or personnel training. 6. Review and approve, require modifications in (to secure approval) or withhold approval of those activities related to the care and use of animals as set forth in the PHS Policy at IV.C. 7. Review and approve, require modifications in (to secure approval) or withhold approval of proposed significant changes regarding the use of animals in ongoing activities as set forth in the PHS Policy at IV.C. 8. Notify investigators and the institution in writing of its decision to approve or withhold approval of those activities related to the care and use of animals, or of modifications required to secure IACUC approval as set forth in the PHS Policy at IV.C.4. 9. Be authorized to suspend an activity involving animals as set forth in the PHS Policy at IV.C.6. E. The procedures which the IACUC will follow to fulfill the requirements set forth in the PHS Policy at IV.B. are: (Describe how the IACUC will fulfill each of the functions set forth in the PHS Policy at IV.B. Include how often the IACUC will meet, how often it will inspect facilities, and how the inspections will take place. Describe the procedures the IACUC will follow to address any concerns, and how recommendations will be developed and forwarded to the Institutional Official. The channels for receiving proposed activities, and for reporting the results of IACUC review of applications and proposals should be addressed.) F. The individual(s) authorized by this institution to verify IACUC approval of those sections of applications and proposals related to the care and use of animals is (insert name of individual). G. The health program for personnel who work in laboratory animal facilities or have frequent contact with animals is: (Describe the institution's occupational health program, including the frequency of tuberculosis tests, if any, requirements for medical examinations, etc. The institution may submit a memorandum or pamphlet (if one exists) which informs animal care and use staff of institutional policies regarding health screening or tests.) H. The total gross number of square feet in each animal facility (including each satellite facility), the species of animals housed therein and the average daily inventory, by species, of animals in each facility. (This information may be provided in an attached chart.) I. The training or instruction available to scientists, animal technicians, and other personnel involved in animal care, treatment, or use are: (Provide a synopsis of the training or instruction available in the humane practice of animal care and use, as well as training or instruction in research and testing methods that minimize the number of animals required to obtain valid results and minimize animal distress.) IV. Institutional Status As specified in the PHS Policy at IV.A.2., as Category 1, all of this institution's programs and facilities (including satellite facilities) for activities involving animals have been evaluated and accredited by the American Association for Accreditation of Laboratory Animal Care. All of this institution's programs and facilities (including satellite facilities) for activities involving animals have also been evaluated by the IACUC and will be reevaluated by the IACUC at least once every six months. - OR - As specified in the PHS Policy at IV.A.2, as Category 2, all of this institution's programs and facilities (including satellite facilities) for activities involving animals have been evaluated by the IACUC and will be reevaluated by the IACUC at least once every six months. The report of the IACUC evaluation has been submitted to (insert name or title of the Institutional Official signing the Assurance) and a copy of the report is attached. The report contains a description of the nature and extent of this institution's adherence to the Guide. Any departures from the Guide are identified specifically and reasons for each departure are stated. Where program or facility deficiencies are noted, the report contains a reasonable and specific plan and schedule for correcting each deficiency. The report distinguishes significant deficiencies from minor deficiencies. Semiannual reports of the IACUC evaluation submitted to the Institutional Official (insert name or title of the Institutional Official signing the Assurance) will also contain a reasonable and specific plan and schedule for correcting each deficiency and distinguish significant deficiencies from minor deficiencies. Semiannual reports of IACUC evaluations will be maintained by this institution and made available to OPRR upon request. V. Recordkeeping Requirements A. This institution will maintain for at least three years: 1. A copy of this Assurance and any modifications thereto, as as approved by PHS. 2. Minutes of IACUC meetings, including records of attendance, activities of the committee, and committee deliberations. 3. Records of applications, proposals, and proposed significant changes in the care and use of animals and whether IACUC approval was given or withheld. 4. Records of semiannual IACUC reports and recommendations as forwarded to (insert name or title of the Institutional Official signing the Assurance). 5. Records of accrediting body determinations. B. This institution will maintain records that relate directly to applications, proposals, and proposed changes in ongoing activities reviewed and approved by the IACUC for the duration of the activity and for an additional three years after completion of the activity. C. All records shall be accessible for inspection and copying by authorized OPRR or other PHS representatives at reasonable times and in a reasonable manner. VI. Reporting Requirements A. At least once every 12 months, the IACUC, through the Institutional Official, will report in writing to the Office for Protection from Research Risks (OPRR): 1. Any change in the status of the institution (e.g., if the institution becomes accredited by AAALAC or AAALAC accreditation is revoked), any change in the description of the institution's program for animal care and use as described in this Assurance, or any changes in IACUC membership. If there are no changes to report, this institution will submit a letter to OPRR stating that there are no changes. 2. Notification of the date that the IACUC conducted its semiannual evaluations of the institution's program and facilities (including satellite facilities) and submitted the evaluations to (insert name or title of the Institutional Official signing the Assurance). B. The IACUC, through the Institutional Official, will provide the OPRR promptly with a full explanation of the circumstances and actions taken with respect to: 1. Any serious or continuing noncompliance with the PHS Policy. 2. Any serious deviations from the provisions of the Guide. 3. Any suspension of an activity by the IACUC. C. Reports filed under VI.A.2. and VI.B. above shall include any minority views filed by members of the IACUC. VII. Institutional Endorsement and PHS Approval A. Authorized Institutional Official Name:____________________________________ Title:_____________________________________ Address:___________________________________ ___________________________________________ ___________________________________________ Phone:______________________________________ Signature:________________________Date:_________ B. PHS Approving Official Name:________________________________________ Title:_______________________________________ Address:_____________________________________ _____________________________________ _____________________________________ _____________________________________ Phone: ____________________________ Signature:___________________ Date:___________ C. Effective Date of Assurance D. Expiration Date of Assurance U.S. GOVERNMENT PRINCIPLES FOR THE UTILIZATION AND CARE OF VERTEBRATE ANIMALS USED IN TESTING, RESEARCH, AND TRAINING The development of knowledge necessary for the improvement of the health and well-being of humans as well as other animals requires in vivo experimentation with a wide variety of animal species. Whenever U.S. Government agencies develop requirements for testing, research, or training procedures involving the use of vertebrate animals, the following principles shall be considered; and whenever these agencies actually perform or sponsor such procedures, the responsible Institutional official shall ensure that these principles are adhered to: I. The transportation, care, and use of animals should be in accordance with the Animal Welfare Act (7 U.S.C. 2131 et. seq.) and other applicable Federal laws, guidelines, and policies(1). II. Procedures involving animals should be designed and performed with due consideration of their relevance to human or animal health, the advancement of knowledge, or the good of society. III. The animals selected for a procedure should be of an appropriate species and quality and the minimum number required to obtain valid results. Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered. IV. Proper use of animals, including the avoidance or minimization of discomfort, distress, and pain when consistent with sound scientific practices, is imperative. Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in other animals. V. Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, or anethesia. Surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents. (Footnote 1: For guidance throughout these Principles, the reader is referred to the Guide for the Care and Use of Laboratory Animals preparted by the Institute of Laboratory Animal Resources, National Academy of Sciences. VI. Animals that would otherwise suffer severe or chronic pain or distress that camot be relieved should be painlessly killed at the end of the procedure or, if appropriate, during the procedure. VII. The living conditions of animals should be appropriate for their species and contribute to their health and comfort. Normally, the housing, feeding, and care of all animals used for biomedical purposes must be directed by a veterinarian or other scientist trained and experienced in the proper care, handling, and use of the species being maintained or studied. In any case, veterinary care shall be provided as indicated. VIII. Investigators and other personnel shall be appropriately qualified and experienced for conducting procedures on living animals. Adequate arrangements shall be made for their in-service training, including the proper and humane care and use of laboratory animals. IX. Where exceptions are required in relation to the provisions of these Principles, the decisions should not rest with the investigators directly concerned but should be made, with due regard to Principle II, by an appropriate review group such as an institutional animal care and use committee. Such exceptions should not be made solely for the purposes of teaching or demonstration. ø U.S. GOVERNMENT PRINTING OFFICE: 1991--294-776